Nicole C Kesty

AstraZeneca | AZ · Medical Affairs

Background Residual risk of relapse remains a substantial concern for breast cancer patients as greater than half of recurrences occur beyond the initial 5y of tamoxifen therapy. First generation multigene signatures provide further prognostic information to standard clinical and pathological factors, however, their utility is strongest for predict...

Introduction: Neoadjuvant chemotherapy increases the likelihood that breast conservation therapy for breast cancer patients will be successful. Breast Cancer Index (BCI), a gene expression assay combining HoxB13/IL17BR ratio and Molecular Grade Index (MGI), is prognostic for the risk of distant recurrence and overall survival in tamoxifen-treated a...

The aim of neoadjuvant chemotherapy is to increase the likelihood of successful breast conservation surgery (BCS). Accurate identification of BCS candidates is a diagnostic challenge. Breast Cancer Index (BCI) predicts recurrence risk in estrogen receptor+lymph node-breast cancer. Performance of BCI to predict chemosensitivity based on pathological...

Breast Cancer Index (BCI) combines two independent biomarkers, HOXB13:IL17BR (H:I) and the 5-gene molecular grade index (MGI), that assess estrogen-mediated signalling and tumor grade, respectively. BCI stratifies early-stage estrogen-receptor positive (ER+), lymph-node negative (LN-) breast cancer patients into three risk groups and provides a con...

2 Background: The MA.17 trial demonstrated that extended adjuvant endocrine therapy with letrozole after 5-y of tamoxifen markedly reduced the risk of recurrence in women with ER+ early stage breast cancer. This trial provides an opportunity to assess the ability of biomarkers to predict late recurrences in ER+ breast cancer. The Breast Cancer Inde...

Accurate determination of cancer origin is necessary to guide optimal treatment but remains a diagnostic challenge. Gene expression profiling technologies have aided the classification of tumors and, therefore, could be applied in conjunction with clinicopathologic correlates to improve accuracy. We report an expanded version of the previously desc...

A dichotomous index combining two gene expression assays, HOXB13:IL17BR (H:I) and molecular grade index (MGI), was developed to assess risk of recurrence in breast cancer patients. The study objective was to demonstrate the prognostic utility of the combined index in early-stage breast cancer. In a blinded retrospective analysis of 588 ER-positive...

573 Background: Breast Cancer Index (BCI), a gene expression assay combining HoxB13/IL17BR ratio and Molecular Grade Index (MGI), is prognostic for the risk of distant recurrence and overall survival in tamoxifen-treated and untreated breast cancer patients. Methods: The objective of this blinded study was to examine whether BCI is significantly as...

Recent progress in targeted cancer therapies for advanced non-small cell lung cancer (NSCLC) has expanded the selection of optimal treatment beyond platinum-based chemotherapy and identified differential response and safety profiles based on histology. Given that accurate pathologic classification is of increasing clinical interest, molecular diagn...

The integrated central actions of hormones secreted from pancreatic islets, the gut and adipocytes regulate both energy homeostasis and body weight. Dysregulation in these neurohormonal pathways probably contributes to pathogenesis of obesity and type 2 diabetes. To examine hormone-based therapies targeting these interrelated pathways as potential...

To assess long-term weight loss efficacy and safety of pramlintide used at different dosing regimens and in conjunction with lifestyle intervention (LSI). In a 4-month, double-blind, placebo-controlled, dose-ranging study, 411 obese subjects were randomized to receive pramlintide (six arms: 120, 240, and 360 microg b.i.d. and t.i.d.) or placebo in...

To characterize the interactive effects of amylin with phentermine or sibutramine on food intake, body weight/composition and gene expression in diet-induced obese (DIO) rats. DIO rats were intraperitoneally injected with a single dose of amylin (10 microg kg(-1)) and/or phentermine (1 mg kg(-1)) or chronically infused with amylin (100 microg kg(-1...

Over the past decade, advances in endocrine and neuro- sciences research have revolutionized our understanding of the biological basis underlying the complex regulation of glucose and energy homeostasis. These advances include not only the discovery and characterization of numerous novel hormones but also a much deeper under- standing of how variou...

Evidence from rodent studies indicates that the beta-cell-derived neurohormone amylin exerts multiple effects on eating behavior, including reductions in meal size, intake of highly palatable foods, and stress-induced sucrose consumption. To assess the effect of amylin agonism on human eating behavior we conducted a randomized, blinded, placebo-con...

In previous 1-yr trials, treatment with pramlintide (120 microg), an analog of the beta-cell hormone amylin, induced sustained reductions in A1C and body weight in insulin-using subjects with type 2 diabetes. To assess the potential of pramlintide as an antiobesity agent, we assessed the weight effect, safety, and tolerability of pramlintide in non...

Pramlintide, an adjunct treatment to mealtime insulin for patients with type 2 and type 1 diabetes, aids glycemic control by suppressing postprandial glucagon secretion, slowing gastric emptying, and enhancing satiety. Because gastric emptying affects oral medication absorption, this placebo-controlled, single-blind, crossover study examined the ab...

Diabetes is a chronic disease affecting > 20 million Americans, and its incidence, especially in the form of type 2 diabetes, is increasing. Multiple therapeutics are available that address the dysregulation of the multiple hormones responsible for glucose homeostasis. Despite the various options,tight glycemic control is often elusive. Additionall...

Extracellular secretion of products is the major mechanism by which Gram-negative pathogens communicate with and intoxicate host cells. Vesicles released from the envelope of growing bacteria serve as secretory vehicles for proteins and lipids of Gram-negative bacteria. Vesicle production occurs in infected tissues and is influenced by environmenta...

Enterotoxigenic Escherichia coli (ETEC) is a prevalent cause of traveler's diarrhea and infant mortality in third-world countries. Heat-labile enterotoxin (LT) is secreted from ETEC via vesicles composed of outer membrane and periplasm. We investigated the role of ETEC vesicles in pathogenesis by analyzing vesicle association and entry into eukaryo...

Gram-negative bacteria shed outer membrane vesicles composed of outer membrane and periplasmic components. Since vesicles from pathogenic bacteria contain virulence factors and have been shown to interact with eukaryotic cells, it has been proposed that vesicles behave as delivery vehicles. We wanted to determine whether heterologously expressed pr...

Typescript. Vita. Thesis (Ph. D.)--Duke University, 2004. Includes bibliographical references (leaves 168-185).